Comparative antimicrobial activity of gatifloxacin tested against Streptococcus spp. including quality control guidelines and etest method validation

Abstract

Gatifloxacin (formerly AM-1155 or CG 5501) is a new 8-methoxy fluoroquinolone with enhanced activity against Gram-positive cocci, especially Streptococcus pneumoniae and other streptococci. Recent clinical strains (599 isolates) were tested against gatifloxacin, three comparison fluoroquinolones, and penicillin by the reference broth microdilution, Etest (AB BIODISK, Solna, Sweden) and standardized disk diffusion methods (5 μg gatifloxacin disk). Gatifloxacin (MIC 90, 0.5 μg/ml) activity was generally comparable to that of trova-floxacin (MIC 90, 0.25 μg/ml), or sparfloxacin (MIC 90, 0.5 μg/ml) and markedly superior to ofloxacin (MIC 90, 2–4 μg/ml) against the streptococci. Rates of penicillin non-susceptibility were 41.9, 38.0, and 16.2% for S. pneumoniae (301 strains), viridans group streptococci (150 strains), and β-haemolytic streptococci (148 strains). Etest results correlated well (95.7–100.0% ± one log 2 dilution) with the reference MIC results, but Etest tended to have elevated gatifloxacin MIC results compared to the broth microdilution method for the highly resistant isolates (MICs, > 2 μg/ml). Gatifloxacin disk zone diameters correlate well to reference MICs for all streptococci and proposed interpretive criteria (susceptible at ≤ 1 μg/ml or ≥ 18 mm, and resistant at ≥ 4 μg/ml or ≤ 14 mm) did not produce discords between method results (absolute agreement). A nine laboratory quality control (QC) study conforming to the National Committee for Clinical Laboratory Standards (NCCLS) Guideline M23-T3 studied S. pneumoniae ATCC 49619 and gatifloxacin. Proposed ranges for QC of NCCLS tests were 0.12–0.5 μg/ml for the broth microdilution test and 24–31 mm for the disk diffusion method. These reported results indicate that gatifloxacin was a potent fluoroquinolone with extensive activity against streptococcal isolates. In vitro test methods to measure this activity appear accurate and comparable; and QC guidelines have been established for routine clinical laboratory use pending approval by the NCCLS and the Food and Drug Administration (FDA).